Abstract
Vitamin D3 hypovitaminosis is associated with several neurological diseases such as Alzheimer’s disease, Parkinson’s disease or multiple sclerosis but also with other diseases such as cancer, diabetes or diseases linked to inflammatory processes. Importantly, in all of these diseases lipids have at least a disease modifying effect. Besides its well-known property to modulate gene-expression via the VDR-receptor, less is known if vitamin D hypovitaminosis influences lipid homeostasis and if these potential changes contribute to the pathology of the diseases themselves. Therefore, we analyzed mouse brain with a mild vitamin D hypovitaminosis via a targeted shotgun lipidomic approach, including phosphatidylcholine, plasmalogens, lyso-phosphatidylcholine, (acyl-/acetyl-) carnitines and triglycerides. Alterations were compared with neuroblastoma cells cultivated in the presence and with decreased levels of vitamin D. Both in cell culture and in vivo, decreased vitamin D level resulted in changed lipid levels. While triglycerides were decreased, carnitines were increased under vitamin D hypovitaminosis suggesting an impact of vitamin D on energy metabolism. Additionally, lyso-phosphatidylcholines in particular saturated phosphatidylcholine (e.g., PC aa 48:0) and plasmalogen species (e.g., PC ae 42:0) tended to be increased. Our results suggest that vitamin D hypovitaminosis not only may affect gene expression but also may directly influence cellular lipid homeostasis and affect lipid turnover in disease states that are known for vitamin D hypovitaminosis.
Highlights
About 85% of the elderly population has vitamin D hypovitaminosis with vitaminD3 serum levels
To investigate if a deficit of calcitriol (1,25-dihydroxyvitamin D3 ), the active form of the fat-soluble vitamin D3, has an influence on lipid homeostasis in brain, we treated human neuroblastoma SH-SY5Y cells for 48 h with 100 nM 1,25(OH)2 vitamin D3 solved in ethanol and compared the changes in the lipid profile to that of cells treated with the solvent control under the same conditions
A sufficient uptake of 1,25-dihydroxyvitamin D3 was verified by an increased gene expression of IL-34, whose transcription is known to be upregulated in SH-SY5Y cells treated with this active form of vitamin D3 [48]
Summary
About 85% of the elderly population has vitamin D hypovitaminosis with vitaminD3 serum levels
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